Early behavioral and catecholaminergic effects of 6-hydroxydopamine and guanethidine in the neonatal rat

New born rats received 7 consecutive daily injections of 6-hydroxydopamine (6-OHDA) or guanethidine. Locomotor activity, measured at 3 day intervals, was differentially affected by these drugs, although neither drug elimination a characteristic pattern of ontogeny of locomotor activity. Differing neurochemical effects were also observed. 6-OHDA decreased tyrosine hydroxylase activity in cortex and cerebellum, increased it in the brainstem and had no effect on the hypothalamus. Guanethidine slightly elevated enzyme levels in all four brain regions, with the elevation in brainstem significant at 16 days of age. Regional brain changes in enzyme activity after 4 daily 6-OHDA injections beginning at 1, 5 or 9 days of age indicated that toxic effect of 6-OHDA upon catecholaminergic neurons was age dependent. These data are not consistent with a simple interpretation either in terms of maturational changes in blood brain barrier permeability to 6-OHDA or neuronal uptake of the drug. Further analyses of brainstem areas indicated that the increased brainstem enzyme activity after 6-OHDA was restricted to the pons.